tbuckley/cabot-search huggingface dataset:
Combined immunodeficiency and impaired PI3K signaling in a patient with biallelic LCP2 variants
Authors: Emily S.J. Edwards, Samar Ojaimi, James Ngui, Go Hun Seo, JiHye Kim, Sanjeev Chunilal, Deborah Yablonski, Robyn E. O’Hehir, Menno C. van Zelm
Journal: Journal of Allergy and Clinical Immunology (2023)

Inborn errors affecting components of the T-cell receptor signaling cascade cause combined immunodeficiency with various degrees of severity. Recently, homozygous variants in LCP2 were reported to cause pediatric onset of severe combined immunodeficiency with neutrophil, platelet, and T- and B-cell defects.We sought to unravel the genetic cause of combined immunodeficiency and early-onset immune dysregulation in a 26-year-old man who presented with specific antibody deficiency, autoimmunity, and inflammatory bowel disease since early childhood.The patient was subjected to whole-exome sequencing of genomic DNA and examination of blood neutrophils, platelets, and T and B cells. Expression levels of the Src homology domain 2-containing leukocyte protein of 76 kDa (SLP76) and tonic and ligand-induced PI3K signaling were evaluated by flow-cytometric detection of phosphorylated ribosomal protein S6 in B and T cells.Compound heterozygous missense variants were identified in LCP2, affecting the proline-rich repeat domain of SLP76 (p.P190R and p.R204W). The patient's total B- and T-cell numbers were within the normal range, as was platelet function. However, neutrophil function, numbers of unswitched and class-switched memory B cells, and serum IgA were decreased. Moreover, intracellular SLP76 protein levels were reduced in the patient's B cells, CD4+ and CD8+ T cells, and natural killer cells. Tonic and ligand-induced levels of phosphorylated ribosomal protein S6 and ligand-induced phosphorylated PLCγ1 were decreased in the patient's B cells and CD4+ and CD8+ T cells.Biallelic variants in LCP2 impair neutrophil function and T-cell and B-cell antigen-receptor signaling and can cause combined immunodeficiency with early-onset immune dysregulation, even in the absence of platelet defects.
Impact of sarcopenia on clinical outcomes for patients with resected hepatocellular carcinoma: a retrospective comparison of Eastern and Western cohorts
Authors: Berend R. Beumer, Kosei Takagi, Stefan Buettner, Yuzo Umeda, Takahito Yagi, Toshiyoshi Fujiwara, Jeroen L.A. van Vugt, Jan N.M. IJzermans
Journal: International Journal of Surgery (2023)

Patient fitness is important for guiding treatment. Muscle mass, as a reflection thereof, can be objectively measured. However, the role of East-West differences remains unclear. Therefore, we compared the impact of muscle mass on clinical outcomes after liver resection for hepatocellular carcinoma (HCC) in a Dutch [the Netherlands (NL)] and Japanese [Japan (JP)] setting and evaluated the predictive performance of different cutoff values for sarcopenia.In this multicenter retrospective cohort study, patients with HCC undergoing liver resection were included. The skeletal muscle mass index (SMI) was determined on computed tomography scans obtained within 3 months before surgery. The primary outcome measure was overall survival (OS). Secondary outcome measures were: 90-day mortality, severe complications, length of stay, and recurrence-free survival. The predictive performance of several sarcopenia cutoff values was studied using the concordance index (C-index) and area under the curve. Interaction terms were used to study the geographic effect modification of muscle mass.Demographics differed between NL and JP. Gender, age, and body mass index were associated with SMI. Significant effect modification between NL and JP was found for BMI. The predictive performance of sarcopenia for both short-term and long-term outcomes was higher in JP compared to NL (maximum C-index: 0.58 vs. 0.55, respectively). However, differences between cutoff values were small. For the association between sarcopenia and OS, a strong association was found in JP [hazard ratio (HR) 2.00, 95% CI [1.230-3.08], P =0.002], where this was not found in NL (0.76 [0.42-1.36], P =0.351). The interaction term confirmed that this difference was significant (HR 0.37, 95% CI [0.19-0.73], P =0.005).The impact of sarcopenia on survival differs between the East and West. Clinical trials and treatment guidelines using sarcopenia for risk stratification should be validated in race-dependent populations prior to clinical adoption.
A comparison of the National Surgical Quality Improvement Program and the Society of Thoracic Surgery Cardiac Surgery preoperative risk models: a cohort study
Authors: Adam R. Dyas, Michael R. Bronsert, William G. Henderson, Christina M. Stuart, Nisha Pradhan, Kathryn L. Colborn, Joseph C. Cleveland, Robert A. Meguid
Journal: International Journal of Surgery (2023)

Cardiac surgery prediction models and outcomes from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) have not been reported. The authors sought to develop preoperative prediction models and estimates of postoperative outcomes for cardiac surgery using the ACS-NSQIP and compare these to the Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS-ACSD).In a retrospective analysis of the ACS-NSQIP data (2007-2018), cardiac operations were identified using cardiac surgeon primary specialty and sorted into cohorts of coronary artery bypass grafting (CABG) only, valve surgery only, and valve+CABG operations using CPT codes. Prediction models were created using backward selection of the 28 non-laboratory preoperative variables in ACS-NSQIP. Rates of nine postoperative outcomes and performance statistics of these models were compared to published STS 2018 data.Of 28 912 cardiac surgery patients, 18 139 (62.8%) were CABG only, 7872 (27.2%) were valve only, and 2901 (10.0%) were valve+CABG. Most outcome rates were similar between the ACS-NSQIP and STS-ACSD, except for lower rates of prolonged ventilation and composite morbidity and higher reoperation rates in ACS-NSQIP (all P <0.0001). For all 27 comparisons (9 outcomes × 3 operation groups), the c-indices for the ACS-NSQIP models were lower by an average of ~0.05 than the reported STS models.The ACS-NSQIP preoperative risk models for cardiac surgery were almost as accurate as the STS-ACSD models. Slight differences in c-indexes could be due to more predictor variables in STS-ACSD models or the use of more disease- and operation-specific risk variables in the STS-ACSD models.
Long‐Lived Photoacid‐Doped Conducting Composites Induce Photocurrent for Efficient Wound Healing
Authors: Haiyan Yin, Huifang Du, Wenya Li, Yinhua Qin, Yonghong Fan, Ju Tan, Mingcan Yang, Chuhong Zhu, Youqian Xu
Journal: Advanced Healthcare Materials (2023)

Electrical stimulation is an effective strategy for facilitating wound healing. However, it is hindered by unwieldy electrical systems. In this study, a light-powered dressing based on long-lived photoacid generator (PAG)-doped polyaniline composites is used, which can generate a photocurrent under visible light irradiation to interact with the endogenous electric field and facilitate skin growth. Light-controlled proton binding and dissociation result in oxidation and reduction of the polyaniline backbone, inducing charge transfer to generate a photocurrent. Due to the rapid intramolecular photoreaction of PAG, a long-lived proton-induced localized acidic environment is formed, which protects the wound from microbial infection. In summary, a simple and effective therapeutic strategy is introduced for light-powered and biocompatible wound dressings that show great potential for wound treatment.
Salvage surgeries for splanchnic artery aneurysms after failed endovascular therapy – case series
Authors: Yi-Chun Lin, Tzu-Chi Liao, Chien-Te Lin, Long-Bin Jeng, Horng-Ren Yang, Chung-Ho Hsu, Wei-Ching Lin, Ching-Feng Wu, Chun-Chieh Yeh
Journal: International Journal of Surgery (2023)

Splanchnic arterial aneurysms are a rare but potentially lethal disease with a mortality rate of more than 10% after rupture. Endovascular therapy is the first-line treatment for splanchnic aneurysms. However, appropriate management for splanchnic aneurysms after failed endovascular therapy remained inconclusive.A retrospective review was performed for consecutive patients (from 2019 to 2022) who underwent salvage surgeries for splanchnic artery aneurysms following failed endovascular therapy. The authors defined failed endovascular therapy as the technical infeasibility to apply endovascular therapy, the incomplete exclusion of the aneurysm, or the incomplete resolution of preoperative aneurysm-associated complications. Salvage operations included aneurysmectomy with vascular reconstruction and partial aneurysmectomy with directly closing of bleeders from the intraluminal space of the aneurysms.Seventy-three patients received endovascular therapies for splanchnic aneurysms, and 13 failed endovascular trials. The authors performed salvage surgeries for five patients and enrolled them in this study, including four false aneurysms of the celiac or superior mesenteric arteries and a true aneurysm of the common hepatic artery. The causes of failed endovascular therapy included coil migration, insufficient space for safely deploying the covered stent, a persistent mass effect from the postembolized aneurysm, or infeasibility for catheter cannulation. The mean hospital stay was nine days (mean±SD, 8.8±1.6 days), with no one suffering 90-day surgical morbidity and mortality, and all patients getting symptoms improvement. During the follow-up period (mean±SD, 24±10 months), one patient suffered a small residual asymptomatic celiac artery aneurysm (8 mm in diameter) and was treated conservatively due to underlying liver cirrhosis.Surgical management is a feasible, effective, and safe alternative for splanchnic aneurysms after failed endovascular therapy.
Author Correction: Proteogenomic landscape of human pancreatic ductal adenocarcinoma in an Asian population reveals tumor cell-enriched and immune-rich subtypes
Authors: Do Young Hyeon, Dowoon Nam, Youngmin Han, Duk Ki Kim, Gibeom Kim, Daeun Kim, Jingi Bae, Seunghoon Back, Dong-Gi Mun, Inamul Hasan Madar, Hangyeore Lee, Su-Jin Kim, Hokeun Kim, Sangyeop Hyun, Chang Rok Kim, Seon Ah Choi, Yong Ryoul Kim, Juhee Jeong, Suwan Jeon, Yeon Woong Choo, Kyung Bun Lee, Wooil Kwon, Seunghyuk Choi, Taewan Goo, Taesung Park, Young-Ah Suh, Hongbeom Kim, Ja-Lok Ku, Min-Sik Kim, Eunok Paek, Daechan Park, Keehoon Jung, Sung Hee Baek, Jin-Young Jang, Daehee Hwang, Sang-Won Lee
Journal: Nature Cancer (2023)
Comment on ‘Toxicities associated with immune checkpoint inhibitors: A systematic study’
Authors: Mohammad-Salar Hosseini, Farid Jahanshahlou
Journal: International Journal of Surgery (2023)

aHematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran bResearch Center for Evidence-Based Medicine, Iranian EBM Center: A Joanna Briggs Institute Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran cAging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Research Center for Evidence-Based Medicine, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, Postal code 5166/15731, EA, Iran. Telephone Number: +984133366581, Fax Number: +984133341994. E-mail address: [email protected], [email protected] (M-S. Hosseini). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Immune microenvironment remodeling after radiation of a progressing brain metastasis
Authors: William H. Hudson, Jeffrey J. Olson, Lisa J. Sudmeier
Journal: Cell Reports Medicine (2023)

Radiation is commonly used in the treatment of many cancers. However, its effects on anti-tumor immune responses are incompletely understood. Here, we present a detailed immunological analysis of two tumors from a patient with multiple non-small cell lung cancer metastases to the brain. One tumor was resected without treatment; the second was irradiated to a total dose of 30 Gy and resected following further progression. Comprehensive single-cell analysis reveals a substantially reduced immune cell fraction in the irradiated tumor, including the depletion of tissue-resident macrophages and infiltration of pro-inflammatory monocytes. Despite the presence of similar somatic mutations in both tumors, radiation is associated with the depletion of exhausted, tumor-resident T cell clones and their replacement by circulating clones unlikely to contribute to tumor-specific immunity. These results provide insight into the local effects of radiation on anti-tumor immunity and raise important considerations for the combination of radiation and immunotherapy.
Trauma system establishment and outcome improvement: a retrospective national cohort study in South Korea
Authors: Junsik Kwon, Myeonggyun Lee, Yoon Kim, Jonghwan Moon, Yo Huh, Seoyoung Song, Sora Kim, Jung-in Ko, Kyoungwon Jung
Journal: International Journal of Surgery (2023)

Trauma is a major cause of mortality, disability, and health care costs worldwide. The establishment of a trauma system is known to solve these problems, but few studies have objectively evaluated the impact of a trauma system on outcomes. Since 2012, South Korea has established a national trauma system based on the implementation of 17 regional trauma centers nationwide and the improvement of the prehospital transfer system. This study aimed to measure the changes in performance and outcome according to the established national trauma system.In this national cohort-based, retrospective follow-up observational study, the authors calculated the preventable trauma death rate (PTDR) by conducting a multipanel review of patients who died in 2015, 2017, and 2019. Furthermore, the authors constructed a risk-adjusted mortality prediction model of 4 767 876 patients between 2015 and 2019 using the extended-International Classification of Disease Injury Severity Scores to compare outcomes.The PTDR was lower in 2019 than in 2015 (15.7 vs. 30.5, P <0.001) and 2017 (15.7 vs. 19.9%, P <0.001) representing 1247 additional lives saved in 2019 compared to that in 2015. In the risk-adjusted model, total trauma mortality was highest in 2015 at 0.56%, followed by that in 2016 and 2017 (0.50%), 2018 (0.51%), and 2019 (0.48%), revealing a significant decrease in mortality over the years ( P <0.001 for trend), representing nearly 800 additional lives saved. The number of deaths for more severe patients with a probability of survival less than 0.25 significantly decreased from 81.50% in 2015 to 66.17% in 2019 ( P <0.001).The authors observed a significant reduction in the PTDR and risk-adjusted trauma mortality in the 5-year follow-up since 2015 when the national trauma system was established. These findings could serve as a model for low-income and middle-income countries, where trauma systems are not yet established.
Letter to the Editor: ELF in the risk stratification of NAFLD—Are the ELF thresholds suggested by the AASLD guidelines appropriate?
Authors: Fredrik Åberg
Journal: Hepatology (2023)

Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki University, Helsinki, Finland List of abbreviations: ELF, Enhanced Liver Fibrosis (ELF); NAFLD, non-alcoholic fatty liver disease; TE, transient elastography Financial support: Dr. Åberg was supported by the Academy of Finland (#338544) and Sigrid Jusélius Foundation. Correspondence Fredrik Åberg, MD, PhD. HUCH Meilahti Hospital, PB 372, 00029 HUS, Finland. Email: [email protected]
Choluresis?
Authors: Richard J. Thompson
Journal: Hepatology (2023)

Institute of Liver Studies, King's College London, London, UK No relevant funding Richard J. Thompson consults for and is on the speakers' bureau for Albireo and Mirum. He consults for and owns stock in Generation Bio and Rectify Pharma. He consults for Alnylam. Correspondence Richard J. Thompson, Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS. Email: [email protected]
Reply: Concurrent large spontaneous portosystemic shunt embolization for the prevention of overt hepatic encephalopathy after TIPS: A randomized controlled trial
Authors: Yong Lv, Guohong Han
Journal: Hepatology (2023)

1Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Centre for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China 2Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an 710032, China Funding: None. Correspondence Guohong Han, Department of Liver Diseases and Digestive Interventional Radiology, Xi'an International Medical Center Hospital of Digestive Diseases, Northwest University, No,777 Xitai Road, High-tech Zone, Xi'an, 710100, China. Email: [email protected]
Reply: Xenogeneic cross-circulation of ex vivo human livers or liver xenotransplantation?
Authors: Wei Kelly Wu, Sophoclis P. Alexopoulos, Matthew Bacchetta
Journal: Hepatology (2023)

1Department of Surgery, Vanderbilt University Medical Center; Nashville, TN, USA 2Transplant Center, University of California Davis Medical Center, Sacramento, CA 3Department of Cardiac Surgery, Vanderbilt University Medical Center; Nashville, TN, USA 4Department of Biomedical Engineering, Vanderbilt University; Nashville, TN, USA Letter to the editor Financial Support: Burroughs Wellcome Fund Physician-Scientist Institutional Award to Vanderbilt University ID: 1018894 (WKW). H. William Scott, Jr Chair in Surgery Foundation (MB). National Institutes of Health grant HL140231 (MB). Congressionally Directed Medical Research Programs PR212237 (MB) Correspondence Matthew Bacchetta, MD, MBA, FACS, FAIMBE, Professor, Department of Cardiac Surgery, Vanderbilt University Medical Center, Medical Center East, 1215 21st Avenue South, Suite 5025, Nashville, Tennessee 37232, USA. Email: [email protected]
Letter to the Editor: Xenogeneic cross-circulation of ex vivo human livers or liver xenotransplantation?
Authors: Burcin Ekser
Journal: Hepatology (2023)

Division of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA Funding: None. Correspondence Burcin Ekser, MD, PhD, Division of Transplant Surgery, Department of Surgery Indiana University School of Medicine, 550 University Blvd, Room 4601, Indianapolis, IN, 46202. Email: [email protected]
Exploiting Cancer Vulnerabilities by Blocking of the DHODH and GPX4 Pathways: A Multifunctional Bodipy/PROTAC Nanoplatform for the Efficient Synergistic Ferroptosis Therapy
Authors: Lang Yao, Na Yang, Wei Zhou, Mahmood Hassan Akhtar, Weiping Zhou, Chang Liu, Shuang Song, Ying Li, Wenzhao Han, Cong Yu
Journal: Advanced Healthcare Materials (2023)

Abstract Ferroptosis is a form of programmed cell death and plays an important role in many diseases. Dihydroorotate dehydrogenase (DHODH) and glutathione peroxidase 4 (GPX4) play major roles in cell resistance to ferroptosis. Therefore, inactivation of these proteins provides an excellent opportunity for efficient ferroptosis‐based synergistic cancer therapy. In this study, a multifunctional nanoagent (BPN pro ) containing a GPX4 targeting boron dipyrromethene (Bodipy) probe (BP) and a DHODH targeting proteolysis targeting chimera (PROTAC) is reported. BPN pro is prepared using a nanoprecipitation method in the presence of a thermoresponsive liposome, where BP is encapsulated inside and the cathepsin B (CatB)‐cleavable PROTAC peptide (DPCP) is modified on the outer surface. In the presence of near‐infrared (NIR) photoirradiation, BPN pro is melted and BP is released in tumor cells. Subsequently, BP inhibits the activity of GPX4 by covalently bonding with the selenocysteine at the enzyme active site. In addition, DPCP achieves sustained degradation of DHODH upon activation by CatB overexpressed in the tumor. The synergistic deactivation of GPX4 and DHODH induces extensive ferroptosis and subsequent cell death. In vivo and in vitro studies clearly show that the proposed ferroptosis therapy provides excellent antitumor effect.
SARS-CoV-2 transmission with and without mask wearing or air cleaners in schools in Switzerland: A modeling study of epidemiological, environmental, and molecular data
Authors: Nicolas Banholzer, Kathrin Zürcher, Philipp Jent, Pascal Bittel, Lavinia Furrer, Matthias Egger, Tina Hascher, Lukas Fenner
Journal: PLoS Medicine (2023)

Background Growing evidence suggests an important contribution of airborne transmission to the overall spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), in particular via smaller particles called aerosols. However, the contribution of school children to SARS-CoV-2 transmission remains uncertain. The aim of this study was to assess transmission of airborne respiratory infections and the association with infection control measures in schools using a multiple-measurement approach. Methods and findings We collected epidemiological (cases of Coronavirus Disease 2019 (COVID-19)), environmental (CO 2 , aerosol and particle concentrations), and molecular data (bioaerosol and saliva samples) over 7 weeks from January to March 2022 (Omicron wave) in 2 secondary schools ( n = 90, average 18 students/classroom) in Switzerland. We analyzed changes in environmental and molecular characteristics between different study conditions (no intervention, mask wearing, air cleaners). Analyses of environmental changes were adjusted for different ventilation, the number of students in class, school and weekday effects. We modeled disease transmission using a semi-mechanistic Bayesian hierarchical model, adjusting for absent students and community transmission. Molecular analysis of saliva (21/262 positive) and airborne samples (10/130) detected SARS-CoV-2 throughout the study (weekly average viral concentration 0.6 copies/L) and occasionally other respiratory viruses. Overall daily average CO 2 levels were 1,064 ± 232 ppm ( ± standard deviation). Daily average aerosol number concentrations without interventions were 177 ± 109 1/cm 3 and decreased by 69% (95% CrI 42% to 86%) with mask mandates and 39% (95% CrI 4% to 69%) with air cleaners. Compared to no intervention, the transmission risk was lower with mask mandates (adjusted odds ratio 0.19, 95% CrI 0.09 to 0.38) and comparable with air cleaners (1.00, 95% CrI 0.15 to 6.51). Study limitations include possible confounding by period as the number of susceptible students declined over time. Furthermore, airborne detection of pathogens document exposure but not necessarily transmission. Conclusions Molecular detection of airborne and human SARS-CoV-2 indicated sustained transmission in schools. Mask mandates were associated with greater reductions in aerosol concentrations than air cleaners and with lower transmission. Our multiple-measurement approach could be used to continuously monitor transmission risk of respiratory infections and the effectiveness of infection control measures in schools and other congregate settings.